XPO1CRM1

XPO1, also called exportin-1 or chromosome region maintenance 1 (CRM1), is a major transport receptor of the karyopherin family that mediates the nuclear export of proteins and ribonucleoprotein particles bearing a leucine-rich nuclear export signal (NES). In the nucleus, XPO1 binds its cargo in complex with RanGTP and ferries it through the nuclear pore complex to the cytoplasm. In the cytoplasm, GTP hydrolysis on Ran leads to cargo release, and XPO1 is recycled back to the nucleus for additional export cycles.

Structurally, XPO1 is a large, HEAT-repeat–rich protein that forms an elongated scaffold able to accommodate diverse NES-containing cargo. The directionality and efficiency of export depend on the RanGTP/RanGDP gradient across the nuclear envelope and on the regulated interaction between XPO1 and its cargo.

Biological significance and clinical relevance: XPO1 is essential for multiple cellular processes, including cell-cycle progression, DNA damage response, and stress signaling, by controlling the subcellular localization of regulatory proteins such as p53, p21, and various transcription factors. Because many cancer cells rely on enhanced nuclear export to inactivate tumor suppressors, XPO1 has emerged as a therapeutic target. Small-molecule inhibitors known as selective inhibitors of nuclear export (SINE) covalently bind XPO1, blocking cargo binding and causing nuclear retention of cargo proteins. Selinexor is the prototype SINE compound and has been studied in hematologic and solid tumors, with clinical use in several indications.